Pharmacokinetic dosing of aminoglycosides: a controlled trial

Bartal, Carmi; Danon, Abraham; Schlaeffer, Francisc; Reisenberg, Klaris; Alkan, Michael; Smoliakov, Rosa; Sidi, Aviel; Almog, Yaniv

doi:10.1016/s0002-9343(02)01476-6

Cited by 136 publications

(79 citation statements)

References 22 publications

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“…The much smaller standard deviation for peak concentration of this group indicates that TDM allows more accurate dose determination, providing more predictable peak concentrations for specific patients. In human patients receiving aminoglycoside antimicrobials in intensive care units, TDM is considered essential because of decreased probability of these patients to achieve therapeutic concentrations at initial doses given 3, 6, 27, 28. The low proportion of peak concentrations >32 μg/mL in our study suggests this applies to our population of equine patients.…”

Section: Discussionmentioning

confidence: 67%

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Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Bauquier

Boston

Sweeney

et al. 2015

Veterinary Internal Medicne

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BackgroundGentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values.ObjectivesDetermine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 μg/mL.AnimalsSixty‐five horses (2002–2010) receiving once‐daily gentamicin with TDM performed (N = 99 sets).MethodsRetrospective study. Data from hospitalized horses including weight, dose, plasma peak, and trough gentamicin concentration, creatinine concentrations and presence of focal or systemic disease were collected from medical records. Peak concentrations measured 25–35 minutes after administration were included (N = 77). Data were divided into low (<7.7 mg/kg), medium (7.7–9.7 mg/kg) and high (>9.7 mg/kg) dose groups, and were grouped by the horse having focal or systemic disease.ResultsPeak concentrations resulting from doses ≥7.7 mg/kg were 5.74 μg/mL (SE 2.1 μg/mL) greater than peaks from doses <7.7 mg/kg (P = .007). Peak concentrations was 3.6 times more likely to be >32 μg/mL if dose was ≥7.7 mg/kg (P = .04). There were no significant effects of dose on trough or creatinine concentration. At a given dose, horses with focal disease had higher peaks than those with systemic disease (P = .039).Conclusions and Clinical ImportanceThese data suggest gentamicin dosage should be individually determined in horses using TDM, but support an initial once‐daily dose of 7.7–9.7 mg/kg IV to achieve peaks >32 μg/mL and trough concentrations <2 μg/mL. Further studies evaluating the safety of doses >6.6 mg/kg are required.

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Section: Discussionmentioning

confidence: 67%

“…The need for TDM and dose adjustments in systemic illness is also emphasized in human medicine. As previously mentioned, TDM of aminoglycosides in human intensive care units is considered essential 3, 6, 27, 28, 33. Further, human studies have shown that volume of distribution in septic patients changes as disease state changes 33.…”

Section: Discussionmentioning

confidence: 98%

Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Bauquier

Boston

Sweeney

et al. 2015

Veterinary Internal Medicne

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“…Amikacin levels measured at 1 h (peak) were considered as the target concentration. The optimal peak was considered as >64 mg/L, whereas the potential toxicity threshold was determined by a C min ≥ 5 mg/L [3,13]. Using the same PK software, the PK parameters of the patients were used to generate a simulation of peak and C min for a 10 mg/kg and 15 mg/kg loading dose of amikacin.…”

Section: Methods and Patientsmentioning

confidence: 99%

“…Data on the occurrence of nephrotoxicity A c c e p t e d M a n u s c r i p t 11 when higher doses of amikacin are used in critically ill patients are scarce. In one study, a group of patients in which amikacin concentrations were monitored in order to target a peak >60 mg/L had a mean C min of 9 mg/L [13]; however, the degree of renal toxicity was similar to that in patients treated with a conventional regimen.…”

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confidence: 99%

Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy

Taccone¹,

Backer²,

Laterre³

et al. 2011

International Journal of Antimicrobial Agents

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“…ODD uses an increased dose for the daily shot and is reported to have an improved efficacy due to concentration-dependent bactericidal activity and also is suggested to minimize the likelihood of developing toxicities comparing to the traditional multiple daily dosing (1,14). However, due to the increased dosage, ODD is more likely to cause an adverse reaction related to endotoxin contamination.…”

Section: Discussionmentioning

confidence: 99%

Augmenting Effect of Antibiotics on Endotoxin Activity May Cause a Safety Problem

Yamamoto

Sakai

Ochiai

et al. 2004

Microbiology and Immunology

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Enhancing/interfering effect of antibiotics on endotoxin was evaluated using the endotoxin test and the cell line assay in 28SC cells that has a responsiveness consistent with that of human peripheral blood. When a total of 21 products of seven different kinds of antibiotics were tested, none showed any significant effect on the endotoxin test at its therapeutic dose. However, aminoglycosides showed a significant augmenting effect on IL‐6 induction of endotoxin in 28SC cells. Detailed examination of the augmenting effect was made on spectinomycin in the in vitro cell line assay and also in the lethal endotoxin challenge assay in D‐galactosamine‐treated mice. Spectinomycin also enhanced the endotoxin lethality in D‐galactosamine‐treated mice. A kinetic analysis in endotoxin‐sensitized 28SC cells revealed that the augmentation takes place as quickly as 10 min after spectinomycin treatment. Accordingly, a special caution concerning the augmenting effect was assumed necessary for the safety control of antibiotic products as well as for selecting antibiotics for the therapeutic use.

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Pharmacokinetic dosing of aminoglycosides: a controlled trial

Cited by 136 publications

References 22 publications

Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy

Augmenting Effect of Antibiotics on Endotoxin Activity May Cause a Safety Problem

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